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Mucopolysaccharidosis VIPhase 2iMProveSNCT03370653

A Study in MPS VI to Assess Safety and Efficacy of Odiparcil

A Phase 2 study testing Odiparcil in people with Mucopolysaccharidosis VI, run by Inventiva Pharma at 4 sites in 4 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

Mucopolysaccharidoses (MPS) are a group of rare inherited disorders characterized by a deficiency of lysosomal enzymes responsible for the normal degradation of glycosaminoglycans (GAGs). Read more about this study

Who is it for?
Ages 16 years and older
Conditions the study is for
Mucopolysaccharidosis VI
What is being tested?
Odiparcil
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
20 participants
Where
4 sitesin 4 countries
Study dates
30 Dec 2017to 22 Oct 2019
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 16 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 1. Patients with MPS Type VI receiving enzyme replacement therapy (Naglazyme) for at least 6 months on the licensed dosage or as per local guidelines.
  • Patients with MPS Type VI not receiving enzyme replacement therapy for the following reasons:
  • Patients previously treated with ERT but have discontinued for more than 3 months either due to medical decision or personal choice
  • Patients allergic to ERT therapy
  • Patients that have had a previous hematopoietic stem cell transplant (HSCT)
  • Patients not treated with ERT i.e. treatment naïve

Who cannot join

  • Use of any investigational product or investigational medical device within 30 days prior to screening. This will include product bought over the counter specifically compounds like genistein and pentosane polysulphate which may not be considered as investigational products by patients and some health care professionals.
  • Concurrent disease or condition that would interfere with study participation or pose a safety concern for example patient with: severe cardiac insufficiency as define NYHA class > II, and severe restrictive chronic respiratory insufficiency as reflected by serum [HCO3-] ≥28 mEq/L.
  • Subjects who had surgery within 3 months before study starts, or for whom surgery is planned during study period.
  • Patient with spinal cord compression requiring surgical intervention.
  • Subjects with the following liver test anomalies: any ALT, AST > 3xULN or bilirubin >1.5xULN (except if Gilbert syndrome) at screening visit.
  • Evidence of an immunosuppressive state, including known HIV infection, agammaglubilinemias, T-Cell deficiencies.
Show all 17Show fewer
  • Subjects with history of chronic infections, including but not limited to subjects with past history of viral hepatitis C, or B, with recent history of serious or life-threatening infection or any current signs or symptoms that may indicate infection at visit V-1 of study as per investigators clinical judgement.
  • History of malignant cancer except of cervical carcinoma in situ, basal cell carcinoma, dermatological squamous cell carcinoma.
  • Subjects with significant haematologic abnormalities, such as haemoglobin <8 g/dL, or WBC<2000 /mm3 or absolute neutrophil count <1300 /mm3, or platelet <30.000 /mm3.
  • International Normalized Ratio (INR), activated partial thromboplastin time (aPTT) or thrombin time (TT) values above the laboratory reference range at screening. For patients on anti-coagulants, they should be within their target effect on INR and be stable.
  • Any history of bleeding diathesis
  • Patient with coexistence of corneal pathologies other than corneal clouding (e.g. exposure keratopathy)
  • An unwillingness on the part of male patients to abstain from sexual intercourse with pregnant or lactating women; or an unwillingness to use highly effective form of birth control if engaging in sexual intercourse with a woman who could become pregnant from the time of the first dose of study medication until completion of follow-up procedures.
  • An unwillingness on the part of female patients to use highly effective form of birth control2 if engaging in sexual intercourse and to have a monthly pregnancy test during treatment and until completion of follow-up procedures.
  • Pregnant or lactating women.
  • Have a known hypersensitivity to any of the ingredients or excipients of the IMP including: Microcrystalline Cellulose, Povidone, Sodium starch glycolate (type A), Magnesium stearate, Opadry™ II 85F18422
  • 1. Previous hematopoietic stem cell transplant (HSCT)

Trial locations and contacts

4 sites in 4 countries.

4 sites in 4 countries

France1 site
  • Hôpital Femme-Mère-Enfant

    Bron, 69500

Other trials in France

Germany1 site
  • Villa Metabolica

    Mainz, 55131

Other trials in Germany

Portugal1 site
  • Centro Hospitalar S. João

    Porto, 4200-319

Other trials in Portugal

United Kingdom1 site
  • Royal Free Hospital

    London, NW3 2QG

Other trials in United Kingdom

About this study

Official title: A Phase IIa Study to Investigate Safety, Pharmacokinetics, and Efficacy of Odiparcil in Patients 16 Years and Above With Mucopolysaccharidosis (MPS) Type VI

Mucopolysaccharidoses (MPS) are a group of rare inherited disorders characterized by a deficiency of lysosomal enzymes responsible for the normal degradation of glycosaminoglycans (GAGs). Medical need for treatment of MPS is still very high due to the poor penetration of the recombinant enzymes into the blood brain barrier as well as the ocular barriers and into tissues that are poorly vascularized, such as cartilages and bones. Odiparcil is an orally active compound that allows the synthesis of soluble glycosaminoglycans (GAGs), mainly chondroitin sulfate (CS) and dermatane sulfate (DS). The neosynthesized solubles GAGs are then excreted in urine. By diverting endogenous GAG synthesis to the synthesis of soluble odiparcil linked GAGs, odiparcil should decrease the intracellular pool of GAGs and consequently decrease the lysosomal GAG accumulation.

The primary objective of the study is to assess the safety and efficacy of two doses of odiparcil in MPS VI patients and to provide evidence to enable the selection of the relevant dose of odiparcil for phase III study. The secondary objective of this study is to characterize the dose response, PK and PD of odiparcil.

Read the detailed description

Study design: This phase IIa study consists of 2 parts performed sequentially: a preliminary safety assessment followed by the core study with a double-blind, randomized, dose-ranged cohort of patients receiving Enzyme Replacement Therapy (ERT) and an open-label cohort of patients not receiving ERT.

Preliminary safety assessment (N=2): open-label, escalating dose (2 doses) study. If acceptable safety profile is achieved, patients will be then included in the open-label arm of the core study.

Core study

Core study will be conducted on 2 populations in parallel:

  • A first cohort (N=18): MPS VI patients receiving ERT assigned in 3 arms:
  • Placebo (N=6)
  • Odiparcil 500 mg per day (250 mg BID) (N=6)
  • Odiparcil 1000 mg per day (500 mg BID) (N=6).
  • A second cohort (N=6): MPS VI patient not receiving ERT (odiparcil 1000 mg per day (500 mg BID)).

Study duration: The overall study duration will be 20 months, including the 10-month enrolment period.

For each patient, the study duration will be:

  • Preliminary safety assessment: 6 weeks including a 4-week run-in period followed by 2-week treatment period. Then, patients will go on treatment period in core study.
  • Core study: 34 weeks including a 4-week run-in period followed by 26-week treatment period and 4-week of follow-up.
Being tested
Odiparcil, Placebo
Keywords
MPS VI, Lysosomal disease, Glycoaminoglycans (GAG), Odiparcil
Medical subject headings
Mucopolysaccharidosis VI

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • OdiparcilDrug

    Investigational product: odiparcil 250 mg tablets

  • PlaceboOther

    Comparator: placebo tablets similar to odiparcil 250 mg tablets

Study groups in NCT03370653
Study groupRoleWhat they receive
Double-blind - odiparcil 1000 mg per dayExperimental2 tablets of odiparcil 250 mg per os, twice daily (BID)
Receives: Drug: Odiparcil
Double-blind - odiparcil 500 mg per dayExperimental1 tablet of placebo and 1 tablet of odiparcil 250 mg per os, twice daily (BID)
Receives: Drug: Odiparcil; Other: Placebo
Double-blind - placeboPlacebo comparator2 tablets of placebo per os, twice daily (BID)
Receives: Other: Placebo
Open Label - odiparcil 1000 mg per dayExperimental2 tablets of odiparcil 250 mg per os, twice daily (BID)
Receives: Drug: Odiparcil

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of patients with modified clinical signs

    Changes in physical examination and vital signs

    Measured: 26 weeks

  2. Number of patients with modified biological values

    Change from baseline in laboratory safety tests (coagulation, liver enzymes and crystalluria) 12-lead-ECG and bone biomarkers.

    Measured: 26 weeks

  3. Incidence of AEs/SAEs

    Incidence of AEs/SAEs, patient withdrawals from study due to AEs/SAEs,

    Measured: 26 weeks

  4. 12-lead ECG

    Change from Baseline in ECG

    Measured: 26 weeks

Secondary outcomes (25)
  1. Mobility: 6-minute walk test

    Change from baseline in 6-minute walk test

    Measured: 26 weeks

  2. Mobility: 9-hole PEG test

    Change from baseline in 9-hole PEG test

    Measured: 26 weeks

  3. Mobility: range of motion of the shoulder

    Change from baseline in range of motion of the shoulder

    Measured: 26 weeks

  4. Pain assessment

    Change from Baseline in Brief Pain Inventory (BPI)

    Measured: 26 weeks

  5. Respiratory function

    Change from Baseline in FEV1

    Measured: 26 weeks

  6. Respiratory function

    Change from Baseline in FVC

    Measured: 26 weeks

  7. Respiratory function

    Change from Baseline in MVV

    Measured: 26 weeks

  8. Cardiac and vascular function

    Change from Baseline in echocardiogram

    Measured: 26 weeks

  9. Cardiac and vascular function

    Change from Baseline in carotid intima media thickness Odiparcil concentration remaining in patient plasma 12 hours following the last intake of investigational product at visits V4 and V7. An identification of odiparcil metabolites in plasma at visit V2.

    Measured: 26 weeks

  10. Audiology assessments

    Change from Baseline in pure tone audiometry

    Measured: 26 weeks

  11. Audiology assessments

    Change from Baseline in whisper voice test

    Measured: 26 weeks

  12. Ophthalmology assessments

    Change from Baseline in corneal opacification

    Measured: 26 weeks

  13. Ophthalmology assessments

    Change from Baseline in level of retinopathy

    Measured: 26 weeks

  14. Ophthalmology assessments

    Change from Baseline in optic nerve involvement,

    Measured: 26 weeks

  15. Ophthalmology assessments

    Change from Baseline in intra-ocular pressure

    Measured: 26 weeks

  16. Ophthalmology assessments

    Change from Baseline in visual acuity

    Measured: 26 weeks

  17. Quality of life questionnaires

    Change from Baseline in EQ-5D-5L questionnaires. 5 dimensions scored on a 5-point scale will be assessed: mobility, self-care, usual activities, pain/discomfort, anxiety/depression

    Measured: 26 weeks

  18. Quality of life questionnaires

    Change from Baseline in Zarit caregiver burden questionnaires. Scale in 22 items scored on a 5-point scale with 0 = never and 5 = nearly always

    Measured: 26 weeks

  19. Quality of life questionnaires

    Change from Baseline in Fatigue Severity Scale questionnaires. 9 questions scored on a 7-point scale with 1 = strongly disagree and 7= strongly agree

    Measured: 26 weeks

  20. Pharmacokinetics: odiparcil concentration in plasma

    Odiparcil concentration in plasma at visit V2 (up to 12 hours post dose).

    Measured: 12 hours

  21. ¨Pharmacodynamics: GAG concentrations

    GAG concentration in leukocytes isolated from peripheral

    Measured: 26 weeks

  22. ¨Pharmacodynamics: GAG concentrations

    GAG concentrations in urine

    Measured: 26 weeks

  23. Pharmacodynamics: GAG concentrations

    GAG concentrations in skin

    Measured: 26 weeks

  24. ¨Pharmacodynamics: anti-thrombin activity IIa

    Change from Baseline in anti-thrombin activity IIa in plasma

    Measured: 26 weeks

  25. ¨Pharmacodynamics: Thrombin Generation Assay (TGA)

    Change from Baseline in TGA in plasma

    Measured: 26 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Dec 2017
  2. Study start30 Dec 2017
  3. Primary completion24 Sep 2019
  4. Study completion22 Oct 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Preliminary safety assessment (N=2): an open-label, escalating dose (2 doses) study. Core study: conducted on 2 populations in parallel: * A first cohort (N=18): MPS VI patients receiving ERT assigned in 3 arms: * Placebo (N=6) * Odiparcil 500 mg per day (250 mg BID) (N=6) * Odiparcil 1000 mg per day (500 mg BID) (N=6). * A second cohort (N=6): MPS VI patients not receiving ERT (odiparcil 1000 mg per day (500 mg BID)).
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
20 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03370653
Sponsor's protocol ID
IVA_01_ODI_HMPS_17_002
Acronym
iMProveS
Status last verified
Oct 2019
First submitted
23 Nov 2017
Last updated
1 Nov 2019
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Odiparcil in people with Mucopolysaccharidosis VI, run by Inventiva Pharma at 4 sites in 4 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 1 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in France, Germany, Portugal, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of patients with modified clinical signs (time frame: 26 weeks). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Nov 2019.

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